title: The risk of hand foot skin reaction to pazopanib, a novel multikinase inhibitor: a systematic review of literature and meta-analysis.
abstract: Pazopanib is a novel multikinase inhibitor that shares a similar spectrum of target receptors with sorafenib and sunitinib. We have performed a systematic analysis to investigate the risk of HFSR to pazopanib and compare the difference in incidence between sorafenib, sunitinib, and pazopanib. Relevant studies were identified from PubMed (1998-2010) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2010. Eligible studies were limited to prospective Phase II-III clinical trials in which cancer patients were treated with pazopanib 800 mg orally once daily. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. A total of 1,163 patients from 10 prospective clinical trials were included in the analysis. The overall incidence of all-grade and high-grade HFSR was 4.5% (95% CI: 2.5-7.9%) and 1.8% (95% CI: 0.7-4.6%), respectively. The relative risks of all-grade and high-grade HFSR to pazopanib monotherapy in comparison with controls were increased for all-grade (RR = 6.09, 95% CI: 1.11-33.36, p = 0.037) and high-grade HFSR (RR = 2.51, 95% CI: 0.12-51.9, p = 0.55). The risk of all-grade and high-grade HFSR to pazopanib was significantly lower as compared to sorafenib and sunitinib (RR = 7.5, 95% CI: 5.5-10.2, p < 0.001; RR = 5.9, 95% CI: 3.5-10.0, p < 0.001 and RR = 4.2, 95% CI: 3.0-5.7, p < 0.001; RR = 3.6, 95% CI: 2.1-6.2, p < 0.001). Despite sharing the same spectrum of target receptors with sorafenib and sunitinib, pazopanib is associated with an unexpectedly low risk of HFSR. Further investigations are needed to elucidate HFSR pathogenesis.
authors.affiliation: Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Rockefeller Outpatient Pavilion Suite 228, 160 East 53rd Street, New York, NY 10022, USA.
authors.forename: Yevgeniy
authors.initials: Y
authors.lastname: Balagula
authors.forename: Shenhong
authors.initials: S
authors.lastname: Wu
authors.forename: Xiao
authors.initials: X
authors.lastname: Su
authors.forename: Darren R
authors.initials: DR
authors.lastname: Feldman
authors.forename: Mario E
authors.initials: ME
authors.lastname: Lacouture
mesh_terms: D060831:Hand-Foot Syndrome / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D015994:Incidence; D007191:Indazoles; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011743:Pyrimidines / Q000009:adverse effects*; D012307:Risk Factors; D012867:Skin / Q000473:pathology; D013449:Sulfonamides / Q000009:adverse effects*
chemical_list: D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib